Venetoclax

Venetoclax, an inhibitor of B-cell lymphoma 2 protein, has been approved for patients with chronic lymphocytic leukaemia (CLL). CLL is a type of cancer affecting B lymphocytes, and may also involve the lymph nodes. In CLL, abnormal B cells multiply too quickly and live too long, leading to accumulation in the blood.

Venetoclax works by blocking BCL-2, a protein in the body that helps these cancer cells survive. Inhibition of this protein reduces the number of cancer cells and may slow the spread of CLL.

Tumour lysis syndrome (TLS) and neutropenia are common side effects. The potency of venetoclax in inducing apoptosis in CLL cells can result in TLS. Regular monitoring of the blood is recommended and it may be advised to give the first dose as an in-patient. Consider prophylactic treatment with allopurinol (starting two to three days prior to venetoclax) or rasburicase in patients with high tumour burden and elevated baseline uric acid levels.

The dose should be tapered up gradually over five weeks to decrease the risk of TLS. The five-week ramp-up schedule starts with a 20mg daily dose with weekly increases to 50 mg, 100 mg, and 200 mg per day to the target dose of 400 mg per day. It is important that the patient continues to remain hydrated throughout treatment drinking 6-8 glasses (approximately 1.7 litres total) of water each day. This is particularly important to start two days before and on the day of the first dose as well as every time the dose is increased.

Venetoclax Tumour by CYP3A4 and is a substrate of P glycoprotein. It is contraindicated with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin) at the start of treatment and during dose titration. Venetoclax increases the toxicity of digoxin and warfarin.